Last update 01 Nov 2024

FXR x CCR5 x CCR2

Last update 01 Nov 2024

Basic Info

Related Targets

FXRCCR5CCR2

Drugs associated with FXR x CCR5 x CCR2

Cenicriviroc mesylate/Tropifexor

Target

CCR2 x CCR5 x FXR

Mechanism

CCR2 antagonists [+2]

Active Org.-

Originator Org.

Novartis Pharma AG

Active Indication-

Inactive Indication

Nonalcoholic Steatohepatitis

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with FXR x CCR5 x CCR2

CTRI/2018/06/014509 / Active, not recruitingPhase 2

A randomized, double-blind, placebo controlled, 3- part,adaptive design, multicenter study to assesssafety, tolerability and efficacy of tropifexor (LJN452) in patients withnon-alcoholic steatohepatitis (NASH) - NASH

Start Date14 Jun 2018

Sponsor / Collaborator

Novartis Healthcare Pvt Ltd.

NCT02855164 / TerminatedPhase 2

A Randomized, Double-blind, Placebo Controlled, 3- Part, Adaptive Design, Multicenter Study to Assess Safety, Tolerability and Efficacy of Tropifexor (LJN452) in Patients With Non-alcoholic Steatohepatitis (NASH): FLIGHT-FXR

The purpose of the study was to assess the effects of different doses of tropifexor (LJN452) with respect to safety, tolerability, and on markers of liver inflammation in patients with NASH

Start Date01 Aug 2016

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with FXR x CCR5 x CCR2

100 Translational Medicine associated with FXR x CCR5 x CCR2

0 Patents (Medical) associated with FXR x CCR5 x CCR2

Literatures (Medical) associated with FXR x CCR5 x CCR2

03 Oct 2021·Expert Opinion on Drug DiscoveryQ3 · MEDICINE

The identification of farnesoid X receptor modulators as treatment options for nonalcoholic fatty liver disease

Q3 · MEDICINE

Article

Author: Ricci, Patrizia ; Zampella, Angela ; Biagioli, Michele ; Distrutti, Eleonora ; Sepe, Valentina ; Baldoni, Monia ; Fiorucci, Stefano

INTRODUCTIONThe farnesoid-x-receptor (FXR) is a ubiquitously expressed nuclear receptor selectively activated by primary bile acids.AREA COVEREDFXR is a validated pharmacological target. Herein, the authors review preclinical and clinical data supporting the development of FXR agonists in the treatment of nonalcoholic fatty liver disease.EXPERT OPINIONDevelopment of systemic FXR agonists to treat the metabolic liver disease has been proven challenging because the side effects associated with these agents including increased levels of cholesterol and LDL-c and reduced HDL-c raising concerns over their long-term cardiovascular safety. Additionally, pruritus has emerged as a common, although poorly explained, dose-related side effect with all FXR ligands, but is especially common with OCA. FXR agonists that are currently undergoing phase 2/3 trials are cilofexor, tropifexor, nidufexor and MET409. Some of these agents are currently being developed as combination therapies with other agents including cenicriviroc, a CCR2/CCR5 inhibitor, or firsocostat an acetyl CoA carboxylase inhibitor. Additional investigations are needed to evaluate the beneficial effects of combination of these agents with statins. It is expected that in the coming years, FXR agonists will be developed as a combination therapy to minimize side effects and increase likelihood of success by targeting different metabolic pathways.

01 Apr 2021·Annals of Translational MedicineQ4 · MEDICINE

Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH)-related liver fibrosis: mechanisms, treatment and prevention

Q4 · MEDICINE

Review

Author: Weiskirchen, Ralf ; Tacke, Frank

Liver fibrosis is the excessive expression and accumulation of extracellular matrix proteins in the liver. Fibrotic scarring occurs as the consequence of chronic injury and inflammation. While the successful treatment of hepatitis B and C reduced the burden of liver disease related to viral hepatitis, non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) are nowadays the leading causes of hepatic fibrosis worldwide. Although basic research activities have significantly advanced our understanding of the molecular disease pathogenesis, the present therapeutic options for fibrosis are still limited. In advanced disease stages, liver transplantation often remains the only curative treatment. This highlights the necessity of preventive strategies to avoid complications of fibrosis, particularly cirrhosis, portal hypertension and liver cancer. Lifestyle modifications (weight loss, exercise, healthy diet) are the basis for prevention and treatment of NAFLD-associated fibrosis. In the present review, we discuss recent advances in antifibrotic prevention and therapy. In particular, we review the current concepts for antifibrotic drug candidates in the treatment of NAFLD and NASH. While some compounds aim at reverting pathogenic liver metabolism, an alternative approach is to disconnect the injury (e.g., NAFLD) from inflammation and/or fibrosis. Investigational drugs typically target metabolic pathways, insulin resistance, hepatocyte death, inflammatory cell recruitment or activation, the gut-liver axis, matrix expression or matrix turnover. While several promising drug candidates failed in phase 2 or 3 clinical trials (including elafibranor, emricasan and selonsertib), promising results with the farnesoid X receptor agonist obeticholic acid, the pan-PPAR agonist lanifibranor and the chemokine receptor CCR2/CCR5 inhibitor cenicriviroc support the expectation of an effective pharmacological therapy for liver fibrosis in the near future. Tackling NAFLD-associated fibrosis from different directions by combinatorial drug treatment and effective lifestyle changes hold the greatest prospects.

02 Jan 2019·Expert Opinion on PharmacotherapyQ3 · MEDICINE

Present and emerging pharmacotherapies for non-alcoholic steatohepatitis in adults

Q3 · MEDICINE

Review

Author: Saito, Satoru ; Imajo, Kento ; Ogawa, Yuji ; Honda, Yasushi ; Nakajima, Atsushi ; Kessoku, Takaomi ; Kobayashi, Takashi ; Yoneda, Masato

INTRODUCTIONMultiple parallel factors are implicated in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH). Currently recommended therapies for NASH include vitamin E and pioglitazone, besides dietary and lifestyle changes.AREAS COVEREDThis review focuses on the clinical development of several emerging drugs for the treatment of NASH and the impact of these drugs on current treatment standards.EXPERT OPINIONFour drug classes (FXR agonists, CCR2/CCR5 antagonists, ASK1 inhibitors, and PPARα/δ agonists) have moved into phase 3 trials for their investigation as NASH treatments. Results from phase 2 trials of other therapeutic agents with other pharmacological actions are also expected. The importance of combinational therapies with synergistic benefits engaging different targets, is now understood. Furthermore, studies have determined that the Mediterranean diet is beneficial for patients with NAFLD, while the traditional Okinawan diet is also considered useful. In the future, it will be important to establish new biomarkers to assess NAFLD activity, furthermore non-invasive diagnostic methods will promote the development of new drugs for NASH.

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